The theme of this PPG is development of improved, cost effective methods for evaluating the human myocardium in ischemic heart disease and for quantitating coronary perfusion reserve as a sensitive technique to assess efficacy of proposed therapeutic interventions. Previous work in development of dynamic quantitative positron emission tomography (PET), radiopharmaceutical tracers and magnetic resonance methods for human heart studies are the basic of the applications presented in this proposal. Project I is non-invasive evaluation of patients with jeopardized heart muscle who will have quantitative PET perfusion studies and fluorodeoxyglucose (FDG) PET before revascularization to test the hypothesis that quantitative perfusion will provide better detection of viability than FDG uptake patterns. Project 1 also proposes a comparison of MRI contrast perfusion methods and mRI functional dynamics to the optional PET method for detection of viability. We hypothesize that in addition to a known modification of peripheral vascular reactivity, the coronary perfuse reserve will be increased by plasma lipid modification therapy. Project 1 also propose studies to show if there is a 20% or greater difference in post menopausal women with or without hormonal replacement. Project II activities have led to the design of a high resolution, high speed cardiac Pet which will have a two-fold improvement in resolution and at lease a five-fold improvement in speed. This instrument prototype is being developed jointly with CTI, Inc. Project II will ring this instrument into operation in 1998 for PPG animal experiments and will incorporate motion compensation and improved 3D reconstruction methods. Project III develops methods of reconstruction, motion compensation and kinetic data analysis. We expect to improve resolution by removal of a 6 mm to 8 mm blurring function due to cardiac and respiratory motion. Kinetic analysis incorporates unique approached involving data extraction from tomographic projections and noise analyses. Project IV provides new radiopharmaceutical chemistry, specifically 18F- labeled mitochondrial probes (rotenone and rhodamine) and new 122-I-labeled PET perfusion agents with some superior attributes relative to other PET agents without the need for a local cyclotron. Project V focuses on metabolism and ion fluxes during heart muscle ischemia and reperfusion in the rat and rabbit heart. This science uses the red cell perfused rabbit heart preparation, tracerkinetics for FDG studies. Data analysis and in particular rapid cardiac data segmentation methods are supplied by Core A and Core C provides radiopharmaceutical to Projects I, and II, and IV. This program project has moved toward application of methods to cardiology problems with the addition of cardiologists and internists involved in patient care to a team of physicists, chemists and engineers.